Poly-a,L-glutamic acid

E Pefferkorn, A Schmitt, R Varoqui. Helix-coil transition of poly(a,L-glutamic acid) at an interface Correlation with static and dynamic membrane properties. Biopolymers 21 1451-1463, 1982. 

HPMA Chlorin e6 copolymer Poly(a-L-glutamic acid) (PGA) Amide bond between drug carboxyl and spacer amine Galactosamine... 

Preparation of poly-a-L-glutamic acid-y-(f-butyl)ester... 

Preparation of N-Capped poly-a-L-glutamic acid General procedure... 

Pharmaceutical formulations consisting of poly-a-L-glutamic acid derivatives were prepared by Bonnet-Gonnet (3) and used in the prolonged release of D,L-a-tocopherol. 

Poly-a-L-glutamic acid derivatives prepared by Piccariello et al. (4) were functionalized with iV-octanoyl-L-triiododiyronine and used in the treatment of thyroid disorders. 

The synthetic polyamino acids are convenient models for chemical studies of proteins since they have the extended polypeptide structure of the proteins but are free from the complications which arise in the proteins from the large number of different side chains. The work described here has been confined to the water-soluble polyamino acids poly-D,L-alanine (PDLA), poly-a,L-glutamic acid (PGA), poly-a,D-glutamic acid, and poly-a,L-lysine, and the polyimino acid, poly-L-proline. 

Optical Inversion of Glutamate Residues in Poly-a,L-glutamic Acid. 

D-Glutamic acid has been detected in samples of poly-a,L-glutamic acid (PGA) irradiated in 1% solution at pH 6.8 (Na salt). The D-glutamic acid was measured in hydrolyzates of the polymer by an enzymic method 36). A specific enzyme, L-glutamate decarboxylase E. coli), converts L-glutamic... 

Table I. d-, l- and Total Glutamic Acid in Poly-a, L-glutamic Acid Irradiated in 1% Solution at pH 6.8 (36)...

The yield of D-glutamic acid from poly-a,L-glutamic acid was very low in the presence of O2 (1 atm.). This can be accounted for by either of the mechanisms discussed above since O2 can combine both with H atoms and with the free radicals formed at the a-carbon atom (see Reactions 20-27). 

The evidence is that for poly-D,L-alanine cross-linking is the predominant process for poly-a,L-lysine chain fracture is predominant, and for poly-a,L-glutamic acid cross-linking predominates below pH 4 and chain fracture above pH 4. It is possible that under all conditions studied here all three polymers undergo partial cross-linking and chain scission hence, pH could either suppress cross-linking at high pH or suppress chain fracture... 

With poly-a,L-glutamic acid, the more marked effect of pH on radiation-induced viscosity changes indicates that in this case there is probably an effect in addition to that found with poly-a,L-lysine and poly-D,L-alanine, and this probably arises from charge repulsion as discussed above. 

In the pH range 4-6, poly-a,L-glutamic acid undergoes a transformation from the a-helix, which is an uncharged, relatively rigid rod, to the random-coil form, in which the side chains are charged and the molecule is... 

Zhang G, Fournier MJ, Mason TL, Tirrell DA (1992) Biological synthesis of mraiodisperse derivatives of poly(a, L-glutamic acid) model rodUke polymers. Macrtunolecules 25 3601-3603... 

Oriented films of poly-a-L-glutamic acid and its esters were examined in 1951 via X-ray analysis by Pauling and Corey [26]. The reflexions related to a spacing of 1.5 A, observed also by other investigators at about the same time, confirmed the existence of an a-helix predicted by Pauling et al. [27] for fibrillar proteins, (see Plate 34). 

Poly(a,L-Glutamic Acid)-Alkyltrimethylammonium Cation Complexes... 

Similar behaviour was found for the pH dependence of the relaxational processes associated with an AO/poly a-L-glutamic acid complex (1), in which an increase in the degree of dissociation, (d.d.) induced by increasing the pH of the buffer system, caused... 

Cationic chitosan/carboxymethylceUulose Cationic chitosan/poly(a,L-glutamic acid)... 

References to polypeptides bearing long alkyl sidechains are almost confined to the esters of poly(a,L-glutamic acid) (PyAG-n) and poly (a or p,L-asparfic acid) (PpAA-n or PaAA-n) whose chemical stmctures are depicted in Fig. 1. In these compounds the alkyl sidechain is connected to the mainchain by a carboxylate group that is directly anchored to the backbone in the case of poly(P-peptide)s and through a methylene or ethylene spacer in poly (a-aspartate)s and poly(a-... 

Figure 15 Chemical stractures of (a) Poly(a,L-glutamic acid)-alkyltrimethylammon-ium cation complexes and (b) Poly(L-lysine)-aIkyl sulfate anion complexes.

Mason et al [30] later measured the CD spectra in steady and streaming solution and showed that the acridine orange complex has the form of a left-handed super-helix bound to the core of the right-handed a-helix of the poly-a-L-glutamic acid (see Figure 6). 

The influence of poly-a-amino-acids on the interpretation of chiroptical properties of other OAP, and the difficulties encountered for this interpretation are well exemplified by the case of a polyacid isolated from Bacillus anthracis poly-7-D-glutamic acid (I), an isomer of the well known poly-a-amino-acid poly-a-L-glutamic acid (II). 

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